@article{661e2920a49541ef846a593a31d8d166,
title = "Effluxing ABC transporters in human corneal epithelium",
abstract = "ATP-binding cassette (ABC) transporters are able to efflux their substrate drugs from the cells. Wecompared expression of efflux proteins in normal human corneal epithelial tissue, primary human corneal epithelial cells (HCEpiC), and corneal epithelial cell culture model (HCE model) based on human immortal cell line. Expression of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1-6 (MRP1-6) and breast cancer resistance protein (BCRP) was studied using quantitative RT-PCR, Western blot, and immunohistochemistry. Only MRP1, MRP5, and BCRP were expressed in the freshly excised human corneal epithelial tissue. Expression of MRP1 and MRP5 was localized predominantly in the basal cells of the central cornea and limbus. Functional efflux activity was shown in the cell models, but they showed overexpression of most efflux transporters compared to that of normal corneal epithelium. In conclusion, MRP1, MRP5, and BCRP are expressed in the corneal epithelium, but MDR1, MRP2, MRP3, MRP4, and MRP6 are not significantly expressed. HCE cell model and commercially available primary cells deviate from this expression profile.",
keywords = "ABC transporters, Cell culture, Cell model, Corneal epithelium, Efflux pumps, HCE, Multidrug resistance transporters, Multidrug resistance- associated proteins, P-glycoprotein, Primary cells",
author = "Vellonen, {Kati Sisko} and Eliisa Mannermaa and Helen Turner and Marika H{\"a}kli and Wolosin, {J. Mario} and Timo Tervo and Paavo Honkakoski and Arto Urtti",
note = "Funding Information: This work was financially supported by the Academy of Finland, the Finnish Cultural Foundation, the South Savo Regional Fund, and the USA National Institutes of Health (EY-14878). We are grateful to Dr. Branimir Sikic (Stanford University School of Medicine, USA), Dr. Susan Cole (Cancer Research Institute, Queen's University, Kingston, Canada), Dr. Piet Borst (Netherlands Cancer Institute, The Netherlands), Dr. John Schuetz (St. Jude Children's Research Hospital, Memphis, USA), Astellas Pharma, Inc. (former Yamanouchi Pharmaceutical Co., Ltd), Dr. Andras Varadi and Dr. Attila Ili{\'a}s (Hungarian Academy of Sciences, Hungary), Dr. Douglas Ross (University of Maryland, Marlene and Stewart Greenebaum Cancer Center, Baltimore, USA), Dr. Jan Taipalensuu and Lucia Lazorova (Uppsala University, Sweden) for providing the plasmids for the real-time RT-PCR measurements. We thank M.Sc. Mika Reinisalo for his advices regarding qRT-PCR standards, M.Sc. Sanna Siissalo for her help in CDCF studies, M. Sc. Tuomas Ryh{\"a}nen for his advices and help in Western blot studies, Dr. M. Suhonen for providing compounds for calcein efflux assay and Leena Pietil{\"a} for technical assistance. Pirjo Karppinen (Silm{\"a}keskus Laser), Dr. Juha Lehtosalo (Helsingin Yksityinen Silm{\"a}sairaala Oy) and Heikki Karinen (Oper Oy) are acknowledged for their kind co-operation with corneal epithelial tissue samples.",
year = "2010",
month = feb,
doi = "10.1002/jps.21878",
language = "English",
volume = "99",
pages = "1087--1098",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley & Sons Inc.",
number = "2",
}